There is an increasing body of data demonstrating a close link between biogenic amines and neuropeptides in the central nervous system. To more clearly define anatomical distributions and relationships and functional interactions of substances within these groups, a series of complementary experiments spanning a broad spectrum of disciplinary approaches is proposed. The studies have the following specific goals: (1) to ascertain the relationship between peptide-sensitive neurons and brain aminergic systems utilizing receptor autoradiographic techniques, chemical lesioning procedures, and turnover measurements; (2) to determine the organization of neurons with the brainstem, combining immunocytochemical tract-tracing and receptor methodologies, focusing on the qualitative aspects of the microcircuitry and efferent connectivities of peptidergic substances and their potential actions and interactions with aminergic neurons; (3) to determine the role played by peptides in translating the influence of stress to modulate activity of the mesocortical and mesolimbic dopamine systems utilizing HPLC with electrochemical detection; (4) to determine how coerulospinal norepinephrine and neuropeptides as well as serotonin and co-released neuropeptides interact to affect motoneuron and interneuron excitability utilizing microiontophoresis and intracellular recording techniques. By employing a multidisciplinary approach that includes techniques of behavioral neuroscience, biochemistry, electrophysiology, neuroanatomy and pharmacology in a tightly integrated group of projects, the program has the opportunity to make significant headway towards an understanding of amine-peptide interaction.